The objective of the Ischemic Heart Disease SCOR program at Duke is to implement and support a multidisciplinary approach to research which is ultimately directed at the reduction of death and disability from coronary heart disease. The SCOR has supported both clinical and fundamental research, and our approach has emphasized the natural continuum from basic research on pathophysiology of ischemia at a cellular level -- to mechanisms of abnormal function at an organ level -- to natural history in patients and better ways of quantitating the variables which influence natural history -- to improved treatment. This supplemental request is consistent with our overall goals and with the approach noted above. The supplement proposes two new projects. One of these is designed to explore the steps in myocardial oxidative phosphorylation in an effort to define the site(s) most sensitive to irreversible injury by hypoxia or ischemia. The second new projet is aimed at further exploration of the enzyme and isoenzyme criteria which reflect myocardial damage and its potential salvage or extension. This supplement also proposes to extend the scope of two ongoing projects. One of these will utilize intra-operative assessment of coronary blood flow and its distribution to test several interventions designed to reduce intraoperative myocardial damage through improvement of coronary perfusion. The second proposal is to extend recently developed radionuclide angina techniques to critically assess the influence of physical conditioning of the angina patient on coronary blood flow during exercise. Thus, all four projects are directly related to the goal of the SCOR, i.e., reducing death and disability from ischemic disease by improving our understanding of the mechanisms of ischemic injury to cells and by developing and evaluating methods which diminish the likelihood or extent of that injury.